Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 7, Issue 36, Pages 20255-20263Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.5b05758
Keywords
nanosomal microassembly; therapeutic enzyme; delivery system; microenvironment; hyperuricemia treatment
Funding
- National Natural Science Foundation of China [30973645]
- Chongqing Education Committee [KJ120321]
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Enzyme therapy has unique advantages over traditional chemotherapies for the treatment of hyperuricemia, but overcoming the delivery obstacles of therapeutic enzymes is still a significant challenge. Here, we report a novel and superior system to effectively and safely deliver therapeutic enzymes. Nanosomal microassemblies loaded with uricase (NSU-MAs) are assembled with many individual nanosomes. Each nanosome contains uricase within the alkaline environment, which is beneficial for its catalytic reactions and keeps the uricase separate from the bloodstream to retain its high activity. Compared to free uricase, NSU-MAs exhibited much higher catalytic activity under physiological conditions and when subjected to different temperatures, pH values and trypsin. NSU-MAs displayed increased circulation time, improved bioavailability, and enhanced uric acid-lowering efficacy, while decreasing the immunogenicity. We also described the possible favorable conformational changes occurring in NSU-MAs that result in favorable outcomes. Thus, nanosomal microassemblies could serve as a valuable tool in constructing delivery systems for therapeutic enzymes that treat various diseases.
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